The cause and pathogenesis of tissue injury in most chronic degenerative diseases of man are unclear, although some of these diseases are clearly linked with slow or persistent viral infections. The objective of work described in this continuation proposal is to study the interactions between virus, virus infected cells and the immune response in clearing virus during acute infection or, alternatively, allowing virus to escape immune surveillance and establish persistent infection. Specifically, researc ongoing or planned within this research proposal (1) evaluates the formation, identification and genetic regulation of virus-antibody immune complexes in the circulation; (2) establishes cloned cytotoxic T lymphocyte (CTL) lines in which to identify virus receptors, molecular mechanisms of membrane lysis, diversity and crossreactivity of CTLs and the structural relationship between H02 antigens and viral antigens on the plasma membrane during cytotoxic assult; (3) examines the genetic basis underlying immunopathologic disease induced by acute and persistent virus infections; (4) studies virus infection of lymphocytes as a model of persistent infection and (5) assays the ability of a persistent virus infection to affect the differentiated ("luxury") function of lymphocytes, i.e., alter the production of specific antibodies made by hybridomas and abrogate the lytic activity of CTLs.